Vildagliptin Modified Release Tablet Formulation
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Solution Overview
Problem
Strong inhibition of dipeptidyl peptidase IV (DPP-IV) activity can exacerbate inflammation in chronic inflammatory conditions and is not always desirable, particularly in patients with diabetes and chronic rhinosinusitis, and existing formulations of DPP-IV inhibitors like vildagliptin are sensitive to moisture, requiring stringent storage conditions and twice-daily dosing, which can reduce patient adherence.
Innovation Solution
A modified/sustained release formulation of vildagliptin, specifically a pharmaceutical tablet formulation comprising vildagliptin, hydroxypropyl methylcellulose, microcrystalline cellulose, and magnesium stearate, designed for direct compression, providing improved stability, reduced moisture sensitivity, and once-daily dosing, enhancing patient compliance and treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immediate release formulation of vildagliptin is used, then DPP-IV inhibition efficacy is achieved, but dosing frequency must be twice daily which reduces patient adherence
Solution Approach 1:
The patent applies the dynamics principle by transitioning from an immediate release formulation requiring twice-daily dosing to a modified release formulation enabling once-daily dosing. The modified release mechanism dynamically controls drug release over time, maintaining therapeutic efficacy while improving patient adherence through reduced dosing frequency.
Solution Approach 2:
The modified release formulation ensures continuous therapeutic action of vildagliptin throughout the dosing interval. By controlling the release rate of the drug from the formulation, therapeutic levels are maintained continuously, providing sustained DPP-IV inhibition efficacy with once-daily administration.
2Quantity of substance
If vildagliptin is formulated with high drug load, then dosage strength is improved, but moisture sensitivity increases requiring stringent storage conditions
Solution Approach 1:
The patent employs composite materials by formulating vildagliptin with specific excipients including microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate. This composite formulation reduces moisture sensitivity while maintaining high drug load, allowing stable storage without stringent moisture control requirements.
Solution Approach 2:
The patent applies parameter changes by optimizing the physical and chemical parameters of the formulation components and their ratios. By adjusting parameters such as excipient selection, particle size distribution, and compression conditions, the formulation achieves high drug load with improved moisture stability.
3Ease of manufacture
If direct compression method is used, then manufacturing simplicity is improved, but formulation development is challenging due to water sensitivity
Solution Approach 1:
The patent extracts water from the formulation process by developing a direct compression method that does not require aqueous binders or granulation steps. This eliminates water exposure during manufacturing, addressing the water sensitivity of vildagliptin while maintaining manufacturing simplicity.
Solution Approach 2:
The formulation uses inexpensive, freely flowing excipients that facilitate direct compression without requiring complex equipment or extensive formulation development. The simple excipient system enables straightforward manufacturing while accommodating the drug's water sensitivity.
Data Source
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AI summary
The subject invention provides a pharmaceutical tablet formulation comprising per unit dosage form e.g. per tablet the following ingredients: (a) a compound as an active ingredient, wherein the compound has a formula: wherein R is substituted adamantyl and n is an integer from 0 to 3 or a pharmaceutically acceptable salt thereof; (b) a hydroxypropyl methylcellulose with an apparent viscosity of 80,000 cP to 120,000 cP (nominal value 100,000 cP) when present in a 1% solution; (c) a microcrystalline cellulose; and (d) a magnesium stearate